This study was designed to assess brain-derived neurotrophic factor (BDNF) as a possible candidate for enhanced cognition in breastfed infants. The study was conducted on 42 infants, 4–6 months old, who were classified according to their feeding pattern into breastfed group, formula-fed group and mixed-feeding group. Each infant was subjected to history taking, clinical examination, estimation of the level of BDNF by Enzyme-Linked Immunosorbent Assay (ELISA) technique and assessment by Bayley scale of infant development-second edition (BSID-II). The current study revealed that breastfed group had higher BSID-II scores followed by mixed-fed group then formula-fed one, yet these results reached statistical significance only in total behaviour rating scale (TBRS) and Motor Quality Percentile rank values. Additionally, breastfed infants had significantly higher values of BDNF when compared to those receiving formula milk. Negative correlations between BDNF and both weight for age and weight for length scores were detected. Furthermore, significant positive correlation was detected between BDNF and TBRS. Regression analysis studies revealed that breastfeeding is the most determinant factor for BDNF, TBRS and Motor Quality Percentile rank values. Serum BDNF levels are significantly higher in breastfed infants and shows positive correlations with the results of BSID-II. Given that simultaneous increase in brain BDNF occurs due to onsite production, transport from the periphery or both, it is prudent to hypothesize that BDNF could be one of the factors responsible for the enhanced cognition detected in breastfed infants.